Project Summary/Abstract Histone acetylation and deacetylation are epigenetic states that can produce simultaneously activation or silencing of specific genes. These post-translational processes have been shown to occur in the brain and to affect gene expression. Our preliminary studies show that there exist basal differences in the overall degree of acetylation of H3K14 and H2b, but not H4, in rats that differ in response to novelty. Indeed, the high responders rats (HR) exhibit higher levels of acetylation of H3K14 and H2b when compared to low responders rats (LR). Interestingly, chronic social defeat, which is an established animal model of depression, induces a differential acetylation of H3K14 and H2b in HR and LR rats. Social defeat decreases the acetylation levels on H3K14 and H2b in HR rats and increases it in the LR rats. Social defeat however decreased the level of acetylation of H4 independently of HR and LR rats. Since HR and LR rats exhibit different emotional responses, with the HR rats more prone to depression-like phenomena, we hypothesize that the epigenetic states described for the H3K14 and H2b contribute to individual differences in response to novelty and to individual differences in response to chronic stress-induced psychopathology.